Lysophosphatidylcholine induces delayed myelination in the juvenile ventral hippocampus and behavioral alterations in adulthood.
Maternal virus infection or maternal polyinosinic-polycytidilic acid injection confers behavioral alterations including deficit in prepulse inhibition on the offspring. We previously found delayed myelination specifically in the early postnatal hippocampus in the polyinosinic-polycytidilic acid-injection model. To test whether the transient delay in myelination in the juvenile hippocampus leads to abnormal behaviors after adolescence, we injected lysophosphatidylcholine, a potent demyelinating agent, into the ventral hippocampus of the 10-day-old rat. The lysophosphatidylcholine treatment yielded hypomyelination at postnatal day 16, but myelination reverted to normal level in the adult rat. Neuronal arrays and morphology were not disturbed in this model. We then performed a battery of behavioral tests on the lysophosphatidylcholine-treated and control PBS-injected rats. The lysophosphatidylcholine-treated rats showed deficit in prepulse inhibition, motor hyperactivity in response to methamphetamine and anxiety-related behaviors, all of which are typical behaviors observed in the maternal infection models. These findings suggest that the timing of myelination in the early postnatal hippocampus is crucial for the proper development of sensorimotor and emotional functions. The lysophosphatidylcholine-treated rat without a gross anatomical defect is useful as a model for psychotic disorders.
Makinodan
Manabu
M
Department of Psychiatry, Nara Medical University, Faculty of Medicine, Japan. mmm@naramed-u.ac.jp
Tatsumi
Kouko
K
Okuda
Hiroaki
H
Manabe
Takayuki
T
Yamauchi
Takahira
T
Noriyama
Yoshinobu
Y
Kishimoto
Toshifumi
T
Wanaka
Akio
A
D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D001523:Mental Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D019965:Neurocognitive Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009483:Neuropsychological Tests; D011605:Psychoses, Substance-Induced / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology
D008244:Lysophosphatidylcholines